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MCB:RNA聚合酶III调控巨噬细胞功能促进肿瘤存活

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摘要 : 近日,来自英国的科学家在生物学期刊Molecular and Cellular Biology在线发表了他们关于RNA聚合酶III调控巨噬细胞功能的最新研究进展。
MCB:RNA聚合酶III调控巨噬细胞功能促进肿瘤存活 近日,来自英国的科学家在生物学期刊molecular and Cellular biology在线发表了他们关于RNA聚合酶III调控巨噬细胞功能的最新研究进展。 研究人员指出,肿瘤微环境中的炎症具有许多促癌症发展效应。特别是肿瘤相关巨噬细胞(TAM)能够产生许多细胞因子,促进恶性肿瘤细胞存活,血管生成以及转移维持肿瘤生长。肿瘤相关巨噬细胞内细胞因子的合成与蛋白质合成过程紧密相关,而蛋白质的翻译过程又依赖于RNA聚合酶III转录形成的众多tRNA。因此研究RNA聚合酶III对肿瘤相关巨噬细胞的功能发挥有何影响具有重要意义。 研究人员发现用来源于细菌细胞壁的脂多糖(LPS)刺激小鼠巨噬细胞能够上调表达tRNA的相关基因的转录。nf-kb是介导炎症信号的一个关键转录因子,LPS处理能够会增强NF-kB的p65亚基与tRNA基因的作用。除此之外,研究人员还发现p65能够直接与RNA聚合酶III复合物中的转录因子TFIIIB相互作用,并且p65过表达会诱导pol III依赖性的转录过程。抑制巨噬细胞内的pol III活性能够阻止巨噬细胞分泌细胞因子并抑制其吞噬作用,这也是巨噬细胞的两个关键功能特征。 这项研究揭示了RNA聚合酶III对巨噬细胞功能的重要调控作用,证明RNA聚合酶III可能对于恶性肿瘤细胞相关的免疫反应具有重要影响。 原文链接:RNA Polymerase III is required for macrophage function Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here we connect these facts by showing that stimulation of mouse macrophages with lipopolysaccharides (LPS) from bacterial cell wall causes transcriptional upregulation of tRNA genes. The transcription factor NF-κB is a key transcription factor mediating inflammatory signals and we go on to report that LPS treatment causes an increased association of the NF-κB subunit p65 with tRNA genes. In addition, we show that p65 can directly associate with the Pol III transcription factor TFIIIB and that overexpression of p65 induces Pol III-dependent transcription. As a consequence of these effects, we show that inhibition of Pol III activity in macrophages restrains cytokine secretion and suppresses phagocytosis, two key functional characteristics of these cells. These findings therefore identify a radical new function for Pol III in the regulation of macrophage function which may be important for the immune responses associated with both normal and malignant cells. 作者:Snail 点击:
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